Effect of age and gender on the pharmacokinetics of grepafloxacin

Abstract

The effects of age and gender on the pharmacokinetics of the oral fluoroquinolone grepafloxacin were examined in 48 healthy middle-aged and elderly individuals, of whom half were male and half were female. Participants were stratified into 4 groups (each with n = 12), aged 40 to 49 years, 50 to 59 years, 60 to 69 years, and > 70 years. All received oral grepafloxacin 600 mg once daily for 7 days, and pharmacokinetic parameters were measured on days 1 and 7. Mean plasma grepafloxacin concentrations were consistently higher in females than in males. Peak concentrations, area under the concentration-time curve, apparent volume of distribution and apparent total clearance (but not renal clearance) differed significantly in females and males. There were no significant gender differences in the elimination half-life values. Further analysis of the data suggests that the gender-related pharmacokinetic differences were primarily due to differences in bodyweight, in particular to differences in lean body mass. The only parameters that changed significantly with age were renal clearance and the proportion of the dose excreted unchanged in the urine, but no clear trend was observed, and there was no correlation with creatinine clearance. We conclude that age and gender have no clinically significant effect on the pharmacokinetics of grepafloxacin. Dose adjustment on the basis of these factors does not therefore seem necessary.